Synthesis, carbonic anhydrase enzyme inhibition evaluations, and anticancer studies of sulfonamide based thiadiazole derivatives

Ali Bahadur; Shahid Iqbal; Saiqa Muneer; Hashem O Alsaab; Nasser S Awwad; Hala A Ibrahium

doi:10.1016/j.bmcl.2021.128520

Synthesis, carbonic anhydrase enzyme inhibition evaluations, and anticancer studies of sulfonamide based thiadiazole derivatives

Bioorg Med Chem Lett. 2022 Feb 1:57:128520. doi: 10.1016/j.bmcl.2021.128520. Epub 2021 Dec 26.

Authors

Ali Bahadur¹, Shahid Iqbal², Saiqa Muneer³, Hashem O Alsaab⁴, Nasser S Awwad⁵, Hala A Ibrahium⁶

Affiliations

¹ Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, South Korea. Electronic address: [email protected].
² School of Chemistry and Materials Engineering, Huizhou University, Huizhou 516007, Guangdong, China. Electronic address: [email protected].
³ School of Chemistry and Molecular Biosciences, University of Queensland, St Lucia, Brisbane 4072, Australia.
⁴ Department of Pharmaceutics and Pharmaceutical Technology, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
⁵ Chemistry Department, Faculty of Science, King Khalid University, P.O. Box 9004, Abha 61413, Saudi Arabia.
⁶ Biology Department, Faculty of Science, King Khalid University, P.O. Box 9004, Abha 61413, Saudi Arabia; Department of Semi Pilot Plant, Nuclear Materials Authority, P.O. Box 530, El Maadi, Egypt.

PMID: 34965467
DOI: 10.1016/j.bmcl.2021.128520

Abstract

The sulfonamide-based thiadiazole derivatives (STDs) with different hydrophobic/hydrophilic substitutions were synthesized to investigate their potentials in carbonic anhydrase inhibition (CAI). The CAI activity of the STDs (4a-4h) and the mechanism of the inhibition kinetics were determined. STD 4f contained both methoxy and Cl groups at benzene ring in STD 4f showed the lowest IC₅₀ value. The molecular docking study confirmed that STDs bind strongly with the active sites of the target protein PDBID 1V9E. With the help of Lineweaver-Burk plots, inhibition kinetics of PDBIR 1V9E protein with STDs were determined. Cytotoxicity was checked against human keratinocyte cell lines and the anticancer properties were determined against MCF-7 cell lines. The electrochemical method was used to investigate the binding study with DNA and CA enzymes. Anticancer studies showed that STDs have weak bonding ability to DNA and strong binding ability with CA. It is concluded that anticancer activity is through CAI rather than by DNA binding.

Keywords: Anticancer studies; Carbonic anhydrase; Inhibition evaluations; Sulfonamides; Thiadiazole.

Publication types

Research Support, Non-U.S. Gov't
Retracted Publication

MeSH terms

Animals
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / metabolism
Antineoplastic Agents / pharmacology*
Biocatalysis
Carbonic Anhydrase II / chemistry
Carbonic Anhydrase II / metabolism
Carbonic Anhydrase Inhibitors / chemical synthesis
Carbonic Anhydrase Inhibitors / metabolism
Carbonic Anhydrase Inhibitors / pharmacology*
Catalytic Domain
Cattle
Drug Screening Assays, Antitumor
Humans
MCF-7 Cells
Molecular Docking Simulation
Protein Binding
Sulfonamides / chemical synthesis
Sulfonamides / metabolism
Sulfonamides / pharmacology*
Thiadiazoles / chemical synthesis
Thiadiazoles / metabolism
Thiadiazoles / pharmacology*

Substances

Antineoplastic Agents
Carbonic Anhydrase Inhibitors
Sulfonamides
Thiadiazoles
Carbonic Anhydrase II